Protection from kappa variant (B.1.617.1) and delta variant (B.1.617.2) by Pfizer-BioNTech or Oxford-AstraZeneca vaccine serum  

A group from University of Oxford, Oxford, UK, etc. has reported on protection from B.1.617.1 and B.1.617.2 by vaccine serum.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218332/

Kappa variant = B.1.617.1 is characterized by two mutations L452R and E484Q in the RBD, and delta variant = B.1.617.2 is characterized by two mutations L452R and T478K in the RBD). The L452R mutation is the common in those variants.

Authors tested neutralization of B.1.617.1 and B.1.617.2 using serum from individuals who had received 2 doses of the BNT162b2 Pfizer-BioNTech or ChAdOx1 nCoV-19 Oxford-AstraZeneca vaccine.

Geometric mean neutralization titers against B.1.617.1 were reduced 2.7-fold (p < 0.0001) relative to the Victoria virus for the Pfizer-BioNTech vaccine serum, and 2.6-fold (p < 0.0001) for the Oxford-AstraZeneca vaccine. The Victoria virus is a Wuhan-related strain isolated early in the pandemic from Australia. For B.1.617.2, titers were reduced 2.5-fold (p < 0.0001) relative to the Victoria virus for the Pfizer-BioNTech vaccine serum and 4.3-fold (p < 0.0001) for the Oxford-AstraZeneca vaccine. Although significant reductions in neutralization titers of sera collected from recipients of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines were observed as such, but make sure that there is no evidence of complete escape from neutralization.  

Serum sphingosine could be a GOOD serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients 

A group from Medical University of South Carolina, Charleston, USA, etc. has reported that reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.
https://www.nature.com/articles/s41598-021-93857-7

There was a slight but significant increase in the levels of sphingosine (p < 0.05) in individuals who are antibody positive (n = 134) compared to negative (n = 130), with sphingosine levels 28.96 versus 23.25 pmol/5 × 10−5 L serum, respectively. And further, COVID-19 patients’ serum sphingosine levels were around 15-fold decreased compared to that of asymptomatic donors from 28.96 to 1.88 pmol/5 × 10−5 L serum, respectively (Sphingosine (Sph), dihydro-sphingosine (dhSph), sphingosine 1-phosphate (Sph-1p)).

From the ROC analysis, a sphingosine threshold (or cut-off) value of 8.2 pmol/5 × 10−5 L resulted in 98.47% (95% CI 94.60–99.73%) sensitivity and 98.51% (95% CI 94.72–99.73%) specificity, suggesting that serum sphingosine level provides a selective and sensitive biomarker to identify symptomatic patients versus asymptomatic donors who are positive for SARS-CoV-2 antibody. It was also found that Sphingosine and dihydro-sphingosine do not appear to monitor the disease’s severity.

It was know that one of the biochemical biomarkers, lactate dehydrogenase (LDH), was highly elevated in symptomatic patients with an increased mortality rate. Interestingly, reduced sphingosine levels observed here were not associated with disease severity in COVID-19 patients. These data might suggest that increased or sustained serum sphingosine levels might prevent COVID-19 disease, while reduced sphingosine could result in enhanced inflammation and symptomatic response in some individuals.   

SARS-CoV-2 Spike enhances ACE2 expression in bronchial epithelium and accelerate infection

A group from Second Military Medical University, Shanghai, China, etc. has reported that SARS-CoV-2 Spike enhances ACE2 expression in bronchial epithelium.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254647/

It was found that the expression of ACE2, the receptor of SARS-CoV-2, was significantly increased in bronchial epithelial cells (BEAS-2B cells) by transfection with SARS-CoV-2 Spike protein. In the figure below, BEAS-2B cells were transfected with empty vector, or SARS-CoV-2-Spike protein constructs, and then the expression of long ACE2, dACE2 and total ACE2 was detected by qRT-PCR. BEAS-2B cells were transfected with empty vector or S protein, and the expression of long ACE2 and dACE2 was detected by Western blot using C-terminal anti-ACE2 antibody (β-actin was used as internal control). 

As SARS-CoV-2 S protein activates IFN-stimulated genes (ISGs) expression, it was examined that whether S protein could induce ACE2 expression by activating JAK-STAT signaling. The phosphorylation and activation of STAT1 and STAT2 were analyzed in Spike protein-overexpressed BEAS-2B cells, and it was found that Spike protein could enhance the phosphorylation of STAT1 at tyrosine 701 and STAT2 at tyrosine 690, thus contributing for their activation. Furthermore, using Fludarabine to inhibit STAT1 activation, the induced long ACE2 expression by Spike protein overexpression was greatly downregulated in BEAS-2B cells. Together, it was concluded that SARS-CoV-2 S protein could induce the receptor long ACE2 expression by activating IFN effector JAK-STAT signaling. 

Epitopes in SARS-CoV-2 S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies 

A group from Fred Hutchinson Cancer Research Center, Seattle, USA, etc. has reported that epitopes in SARS-CoV-2 S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
https://pubmed.ncbi.nlm.nih.gov/34237283/

From 198 antibodies isolated from four COVID-19+ convalescent patients, 14 SARS-CoV-2 neutralizing antibodies were isolated. One targeted the N-terminal domain (NTD), one recognized an epitope in S2, and 11 bound the receptor-binding domain (RBD), and those IC50s ranged from 0.007 μg/ml to 15.1 μg/ml.

The S2 subunit contains at least one epitope that, although poorly immunogenic, is present on four of five human beta coronaviruses SARS-CoV-1, SARS-CoV-2, OC43, HKU1). That epitope, as defined by its recognition by CV3-25, is a valid candidate for the development of a global coronavirus vaccine. IC50 of C3-25 against SARS-CoV-2 was 0.34 μg/ml.

Characteristics of  mAbs induced in convalescent patients with COVID-19 against SARS-CoV-2 variants

A group from Joint Research Center for Human Retrovirus infection, Kumamoto University, Japan, etc. has reported that mAbs induced in convalescent patients with COVID-19 and with high affinity for the SARS-CoV-2 RBD efficiently cross-neutralize B.1.351 and P.1.
https://pubmed.ncbi.nlm.nih.gov/34237284/

1102 kinds of IgGs were obtained from two COVID-19 covalescent patients who were infected with SARS-CoV-2 in March, 2020. Among these, 88 kinds bound SARS-CoV-2 Spike, and its 10% bound RBD, and further, IgGs showing neutralizing activity were 5 kinds.

Obtained 5 IgGs: one IgG targeting NTD = 6-74, four IgGs targeting RBD = 3-5, 8-92, 9-105, 10-121.

The neutralization potency of mAbs was examined against pseudoviruses expressing S proteins from the emerging SARS-CoV-2 variants, B.1.1.7, B.1.351, P.1, and mink cluster 5 . Most mAbs neutralized B.1.1.7 and mink cluster 5 variants at the same level as the prototypic 614G pseudovirus. B.1.1.7 was slightly resistant to mAbs 6-74 (3.3-fold) and 3-5 (6.0-fold). The NTD-targeting mAb 6-74 was not effective against mink cluster 5. Neutralization resistance was observed for P.1 and especially B1.351. P.1 was not neutralized by mAbs 6-74 and 3-5 and required a high concentration of the other mAbs (2.6- to 8.0-fold). B.1.351 was neutralized by mAbs 9-105 and 10-121, but not by mAbs 6-74, 3-5, and 8-92. The potencies of 9-105 and 10-121 were reduced against B.1.351 (6.0- and 19-fold, respectively).

All of the variants tested showed resistance to 6-74, suggesting that variants can easily escape from this mAb targeting the NTD, perhaps due to mutations in the NTD. The efficacy of the RBD-targeting mAbs was decreased against P.1 and B.1.351, suggesting that the K417N/T, E484K, and N501Y mutations in the RBD region are critical for the resistance of these variants. Analysis of single mutants revealed that K417N and K417T were critical for escape from 3-5 and slightly decreased the potency of 8-92. E484K and N501Y single mutation did not confer resistance to these RBD-targeting mAbs. However, pseudoviruses with triple RBD mutations, especially the combination of K417N, E484K, and N501Y, were resistant to 3-5, 8-92, and 10-121. Interestingly, the potency of 9-105 was affected by K417N single mutation but neutralized triple mutants at the same level as prototype pseudovirus. It is important to monitor the emergence of new variants and identify the mutations associated with immune escape.
 

Distribution of vaginal Bacterial lectin folds and the folding molecular structures 

Let me introduce you vaginal bacterial lectin folds summarized by a group of University Grenoble Alpes, France, etc..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206207/

Distribution of vaginal bacterial lectin folds was derived from UniLectin3D database. A total of 35 distinct folds were identified in the 2278 UniLectin3D entries. The folding molecular structures of top 6 lectin folds and the distribution are shown below.

β-Sandwich/pili and adhesins fold=22.4%,
α/β OB fold=16.9%,
β-Trefoil fold=14.5%,
β-Sandwich/2 calcium lectin fold=13.4%,
β-Propeller fold=6.6%,
β-Sandwich with galactose-binding domain-like fold=6.6%,
others=19.5%

Effects of mutations on the furin cleavage site (PRRAR) of SARS-CoV-2: P681H and P681R

A group of Cornell University, USA, has reported the effect of P681R mutation on the furin cleavage site of SARS-CoV-2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259907/

The A.23.1 variant has the following Spike mutations: F157L, V367F, Q613H, R102I, L141F, E484K, and P681R. Authors focused on the P681R point mutation, and found that the acquisition of the P618R mutation significantly increase cleavability by furin, with increases beyond that seen for WT as shown below.

To date, the most prevalent SARS-CoV-2 variant has been B.1.1.7. This variant is characterized by a P681H mutation in the spike S1/S2 “furin cleavage site” and has been linked to increased transmissibility due to the presence of the additional basic amino acid, histidine (H). Most recently, a new variant B.1.617.2 has replaced B.1.1.7 as the dominant circulating virus globally, which has a P681R point mutation, and is more conventionally “polybasic” in the S1/S2 cleavage motif and suggested to enhance transmissibility and pathogenesis.
The A.23.1 variant pre-dated B.1.617 contains P681R mutation as mentioned above, and emerged in Uganda beginning in October 2020, to become the dominant virus in the country (89% prevalence on January 12th 2021). However, during the late spring of 2021, A.23.1 became extinct (1% prevalence on May 5th 2021), being replaced by other variants B.1.351 and B.1.525 (without P681R), and increasingly B.1.617.2—which contains P681R.

Overall, this suggests that while the P681R point mutation is important for furin-mediated cleavage, it is not the primary driver of virus transmissibility. 

Man-specific lectins showing anti-viral properties against SARS-CoV-2, SARS-CoV, and MARS-Cov: Legume lectins for SARS-CoV-2

A group from Université Paul Sabatier, Toulouse, France, etc. has reported on Man-specific lectins showing anti-viral properties against SARS-CoV-2, SARS-CoV, and MARS-Cov.
https://www.mdpi.com/2073-4409/10/7/1619/htm

Man-specific lectins from plants, algae, fungi, and bacteria, have been largely studied with respect to their anti-viral properties against different types of enveloped viruses, including HIV-1, papilloma virus, herpes virus, hepatitis C virus, and Ebola virus. In this respect, the algal lectin griffithsin, the cyanobacteria lectins cyanovirin, actinohivin, and microvirin, and various GNA-related lectins like NPA and ASA have been particularly well documented. Most of these Man-specific lectins prevent the virus replication, at least under in vitro conditions, by interfering with the Man-containing N-glycans present on the cell surface of the virion envelope.

Glycans of the S-glycoproteins forming the spikes of SARS-CoV, MERS-CoV and SARSCoV-2, consist of high-mannose glycans and often sialylated N-glycans that predominantly occupy their N-glycosylation sites. However, depending on the coronaviruses, some discrepancies occur between the distribution of the two types of glycans on the surface of the virion, which introduces some diversity in the glycan shield covering the coronavirus spikes.


Figure explanation: Sites containing (almost) exclusively complex glycans (colored red), high-mannose glycans (colored green), and hybrid glycans (colored magenta). Sites harboring a mixture of complex glycans, high-mannose glycans, and a few hybrid glycans (pink), predominant high-mannose glycans (pale green) and predominant complex glycans (orange). In the case of SARS-CoV-2, high-mannose glycans consist essentially of tri-antennary glycans GlcNAc2-Man5–9, but the major high-mannose structure seems to be GlcNAc2Man5.

Accordingly, Man-specific lectins from plants, algae, fungi, and bacteria, which differ slightly due to their fine sugar-binding specificities, offer a vast panel of glycan probes more or less adapted to the specific recognition of the different coronaviruses. In this respect, GNA-related lectins together with Man-specific lectins from algae and cyanobacteria, appear as glycan probes nicely adapted to the recognition of the high-mannose shield which predominates at the top of the MERS-CoV spike. Otherwise, legume lectins with a higher affinity for N-glycans possessing the trimannoside Manα1,3Manα1,6Man core, seem better adapted to the recognition of the N-glycans distributed predominantly at the top of the glycan shield from SARS-CoV and SARS-CoV-2. 

Sero-positivity and neutralizing activity of SARS-CoV-2 infected individuals over one year

A group from Huazhong University of Science and Technology, Wuhan, China, etc. has reported on sero-positivity and neutralizing activity of SARS-CoV-2 infected individuals over one year.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242354/

A total of 162 serum samples from 76 SARS-CoV-2-infected individuals including some of the very earliest COVID-19 patients were collected in our study.

The SARS-CoV-2 Spike- and Nucleocapsid-specific IgM started at intermediate to high levels (96.8 and 54.8%, respectively) early after infection and rapidly and dramatically waned over time. At the end of the one-year observation period, only four cases remained positive for both anti-S and anti-N IgM, resulting in residual positivity rates of 5.3% and 1.3%, respectively. Conversely, the overall sero-positivity for IgG antibodies in convalescent individuals remained very stable with 90.8% and 88.2% sero-positivity for anti-S and anti-N IgG, respectively, persisting for one year

SARS-CoV-2-specific neutralizing activity was measured by virus neutralization assays. The results showed that the majority of patients (57.5%) did not exhibit detectable neutralization capacities one year after the symptom onset. The proportion of patients with high titers of neutralizing antibodies (defined by titers exceeding 1:160) was highest 3-4 months after symptom onset. Among the minority of patients who still had detectable nAb (42.5%), most individuals showed rather low nAb titers (≤1:80). Only very few (5.5%) patients exhibited strong neutralizing titers at or above 1:320.

A role of CD147 in SARS-CoV-2 infection 

A group from Milano University Medical School, Milano, Italy, etc. has reported a role of CD147 in SARS-CoV-2 infection.
https://www.mdpi.com/2073-4409/10/6/1434

CD147 belongs to the Ig superfamily, and it is expressed in several tissues. CD147 has been reported to play an important role in HIV-1, HCV, HBV, and Kaposi’s sarcoma-associated herpesvirus (KSHV) infections. It is known that cyclophilin A (CyPA) partakes in target cells invasion by HIV-1 and SARS-CoV, as the ability of these viruses to infect host cells depends on the interaction between CD147 and CyPA. At the end of 2020, it was first reported that SARS-CoV-2 Spike protein interacts with the host cell receptor CD147.

Taking these background into consideration, authors investigated what really CD147 is doing in SARS-CoV-2 infection.
The blocking Ab (α-CD147 Ab) or equivalent mouse IgG (as isotype control) did not impair SARS-CoV-2 infection ability, suggesting that CyPA binding to CD147 does not play a role in virus entry.

Silencing of CD147 using CD147 siRNA reduced viral entry into pulmonary cells via the reduction of the levels of expression of ACE2, suggesting that CD147 plays an important role in SARS-CoV-2 infection either directly or indirectly, by means of its ability to regulate ACE2 expression at the post-translational level.